{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T14:12:41Z","timestamp":1771596761219,"version":"3.50.1"},"reference-count":61,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: The pathways mediating the beneficial effect of tibial stump preservation for anterior cruciate ligament (ACL) reconstruction remain insufficiently clarified. This study investigated key vascular, neural, and stromal aspects of cellular remodeling processes occurring across lesion stages in tibial remnant pre-reconstruction. Materials and Methods: Biopsies were obtained from 25 patients undergoing arthroscopic ACL reconstruction (paired free-end and tibial insertion sampling) and 10 from quasi-normal, macroscopically intact ligaments (controls). We evaluated intergroup differences in microvascular density using a t-test. Group comparisons for angiogenesis (CD34), neural components (S100, neurofilament-associated proteins\u2014NFAPs), and stromal activation (vimentin and actin) were conducted using Chi-square or Fisher\u2019s exact tests. Results: ACL remnants revealed a significantly higher microvascular density (37 \u00b1 2.3 vs. 18 \u00b1 3.2 vessels\/mm2, p &lt; 0.001), in addition to a markedly increased prevalence of synovial angiogenesis (90% vs. 20%, p &lt; 0.001), stellate stromal cells (94% vs. 10%, p &lt; 0.001), and CD34-positive fibrocytes (92% vs. 10%, p &lt; 0.001) compared to control tissues. Elevated intraligamentous neovascularization (with borderline significance) was also found in these tissues (38% vs. 0%, p = 0.045). Both injured and control ACLs showed widespread S100-positive neural fibers, suggesting maintained Schwann cell integrity despite ligament disruption. In contrast, control ligaments showed a substantially richer NFAP+ neural network, particularly in small-caliber fibers and free nerve endings, pointing to preferential vulnerability of small-caliber neural elements during ACL rupture. Vimentin expression changes\u2014from homogeneous fibrocytic staining to diffuse reticular overexpression in fibrotic lesions\u2014were accompanied by the emergence of stellate myofibroblast-like cells, supporting advanced stromal remodeling. Absent in controls, actin immunoreactivity increased with lesion severity, indicating a progressive myofibroblastic response driven by perivascular cells during ligament remodeling. Conclusions: The tibial ACL remnant is a biologically active, compartmentalized repair niche driven by coordinated vascular, neural, and stromal responses, with reparative activity concentrated at the synovial\u2013epiligament interface. These findings support the biological rationale for preserving tibial remnant for ACL reconstruction.<\/jats:p>","DOI":"10.3390\/medicina62020407","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T13:08:23Z","timestamp":1771592903000},"page":"407","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Histological and Immunohistochemical Characterization of the Tibial ACL Remnant: Implications for Ligament Healing"],"prefix":"10.3390","volume":"62","author":[{"given":"Sorin","family":"Florescu","sequence":"first","affiliation":[{"name":"Discipline of Orthopedics-Traumatology, Department XV, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square No. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6528-7733","authenticated-orcid":false,"given":"Blidi\u015fel Iulian","family":"Alexandru","sequence":"additional","affiliation":[{"name":"Department of Surgery I\u2013Clinic of Surgical Semiotics & Thoracic Surgery, Center for Hepato-Biliary and Pancreatic Surgery, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square No. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8042-0966","authenticated-orcid":false,"given":"George Andrei","family":"Dr\u0103ghici","sequence":"additional","affiliation":[{"name":"Research Center for Pharmaco-Toxicological Evaluations, Faculty of Pharmacy, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square No. 2, 300041 Timi\u0219oara, Romania"},{"name":"Faculty of Pharmacy, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square No. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Drago\u015f Vasile","family":"Nica","sequence":"additional","affiliation":[{"name":"Research Center for Pharmaco-Toxicological Evaluations, Faculty of Pharmacy, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square No. 2, 300041 Timi\u0219oara, Romania"},{"name":"The National Institute of Research\u2014Development for Machines and Installations Designed for Agriculture and Food Industry (INMA), Bulevardul Ion Ionescu de la Brad 6, 077190 Bucure\u0219ti, Romania"},{"name":"Dental Research Center Using Conventional and Alternative Technologies, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square No. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1725-3749","authenticated-orcid":false,"given":"Boru","family":"Casiana","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cVasile Goldi\u0219\u201d Western University of Arad, Bulevardul Revolu\u021biei 94, 310025 Arad, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cosmin Gra\u021bian","family":"Damian","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cVasile Goldi\u0219\u201d Western University of Arad, Bulevardul Revolu\u021biei 94, 310025 Arad, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s40634-018-0136-6","article-title":"Anterior cruciate ligament repair\u2014Past, present and future","volume":"5","author":"Mahapatra","year":"2018","journal-title":"J. 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